tbuckley/cabot-search huggingface dataset:
Abstract P339: The Clinical Application and Ancestral Diversity of Cardiometabolic Polygenic Risk Scores
Authors: Jobanjit S Phulka, Mishal Ashraf, Beenu K Bajwa, Guillaume Pare, Zachary Laksman
Journal: Circulation (2023)

Introduction: A polygenic risk score (PRS) is derived from a genome-wide association study (GWAS) and represents an aggregate of thousands of single-nucleotide polymorphisms (SNPs) that provide a baseline estimate of an individual’s genetic risk for a specific disease or trait at birth. Cardiometabolic disease represents a set of disease processes that historically have disproportionally affected underrepresented racial and minority groups. Furthermore, these groups represent a population generally not well captured by traditional risk scores compared to European cohorts. Since the first GWAS studying myocardial infarction was published, PRSs have increasingly been seen as a promising tool to improve risk stratification of non-European populations. However, how PRSs can be best used in clinical practice remains unclear. Hypothesis: We provide an overview of the PRSs related to cardiometabolic disease, analyze the ancestral diversity of GWAS cohorts, and discuss the evidence supporting their clinical applications. Methods: The Preferred Reporting Items For Systematic Reviews and Meta-analysis extension for Scoping Reviews protocol was used to conduct a scoping review of the MEDLINE, EMBASE, and CENTRAL databases. English studies that published a PRS related to atrial fibrillation (AF), cerebrovascular disease (CVD), coronary artery disease (CAD), dyslipidemia, heart failure, heritable cardiomyopathy, hypertension, and type 2 diabetes were reviewed. Results: Across the 4,863 studies screened, 82 articles met the inclusion criteria. The most common PRS related to CAD, followed by hypertension and CVD. Limited ancestral diversity was observed as most studies (56) included only individuals of European ancestry. A smaller proportion of studies (16) published PRSs derived in multi-ancestry cohorts. Only ten studies published a PRS derived solely from a sample population of non-European ancestry (Chinese, East Asian, Japanese, and Korean). The predictive performance of most PRSs was similar to or superior to traditional risk factors. More than half of the included studies (42) reported an integrated risk model combining a PRS with traditional risk factors or a clinical risk tool (FRS, PCE, CHADS2). The integrated risk model consistently improved predictive accuracy, but few studies investigated the performance in a non-European population. Conclusion: In conclusion, this scoping review reports strong evidence for the clinical use of PRSs in AF, CAD, CVD, and hypertension. However, most PRSs are derived in cohorts of European ancestry, which contributes to a lack of PRS transferability across different ancestral groups, likely exacerbating health inequities. Future prospective studies should focus on further establishing the clinical utility of PRSs. Additionally, diversity in future GWAS cohorts is essential to ensure that PRSs reflect the multi-ancestry society at large.
Abstract P668: Age at Menarche, Adulthood Body Mass Index and Risk of Subclinical Atherosclerosis: A Mendelian Randomization Study
Authors: Devendra Meena, Jian Huang, Abbas Dehghan, Ioanna Tzoulaki
Journal: Circulation (2023)

Earlier age at menarche has been associated with an increased risk of cardiovascular diseases. It has been hypothesized that this association maybe mediated by higher body mass index which is in turn associated with earlier age at menarche. We performed a Mendelian randomization (MR) study to estimate the potential causal effect of age at menarche on carotid artery intima media thickness (cIMT; a marker of subclinical atherosclerosis), and the potential role of body mass index (BMI).Instrumental variables (IVs; P&lt;5e-8) for age at menarche and BMI were obtained from ReproGen consortium (n=370,000 European women) and Neale Lab (n=194,174 European women), respectively. Genetic associations of the identified IVs with cIMT were obtained from our GWAS on cIMT among female participants in UKB. We used the inverse-variance weighted (IVW) method as the primary analysis and weighted median, MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MR-Lasso as sensitivity analyses. In addition, we used Steiger filtering to identify IVs that explain more variance in the exposure than the outcome.We found that an earlier age at menarche was associated with higher cIMT (β IVW =-0.01, P=0.002, 95%CI -0.016 to -0.004). After excluding invalid IVs identified using Steiger filtering and MR-PRESSO, this association was consistent using weighted median, MR-Egger, and MR-Lasso sensitivity methods. Similarly, an earlier age at menarche was also associated with lower adulthood BMI (β IVW =-0.109, P=3.15E-20, 95%CI -0.132 to -0.085). In the multi-variable MR (MVMR), age at menarche was not associated with cIMT after adjusting for adulthood BMI, but adulthood BMI was positively associated with cIMT after adjusting for AAM (β MVMR-IVW =0.02, P=0.004, 95%CI 0.005 to 0.027) suggesting that the effect of AAM on cIMT is partially mediated by adulthood BMI (% of mediation=21.8%).Our study suggests an earlier age at menarche as a potential causal risk factor for subclinical atherosclerosis. We also highlight that the effect of age at menarche on cIMT is potentially mediated by higher adulthood BMI.
Abstract P200: Cumulative Circulating Branched Chain Amino Acid Exposure in Young Adulthood and Incident Atherosclerotic Cardiovascular Disease (ASCVD) in Later Life: The CARDIA Study
Authors: Konrad T Sawicki, Hongyan Ning, Keenan Fine, James D Otvos, Mercedes R Carnethon, Ravi V Shah, Venkatesh L Murthy, John T Wilkins
Journal: Circulation (2023)

Introduction: Circulating branched chain amino acid (BCAA) levels are associated with the development of diabetes mellitus (DM) and downstream ASCVD in middle-aged women. It is unknown if BCAAs in young adult men and women are associated with ASCVD events. BCAA levels may be dynamic in middle-aged adults prior to the development of DM or ASCVD events, thus cumulative BCAA measures in early life may better quantify exposure risk than a single measure at mid-life. Methods: We measured plasma BCAA levels in 3110 Coronary Artery Risk Development in Young Adults study participants using nuclear magnetic resonance (NMR) at Years (y) 2, 7, 15, and 20. To minimize missingness bias, BCAA levels were imputed for the residual 1835 participants without NMR measures. Cumulative BCAA exposure from 19-40y of age was calculated as the area under the curve using a spline-based mixed-effects model to estimate subject-specific BCAA trajectories from 19-40y. Sex-specific associations between cumulative BCAA exposure and incident ASCVD events after 40y of age were assessed by multivariable (Table) Cox proportional hazards regression models including BCAA levels and fasting blood glucose (FBG) at age 40y and further stratified by DM status. Results: Among 4945 participants (55.3% female), there were 255 ASCVD events and 675 DM cases over a median of 18.8 years of follow-up after age 40y. In adjusted models, cumulative BCAA exposure from 19-40y was associated with ASCVD events after 40y of age in women, but not men (Table). The associations in women were robust to adjustment for BCAAs and FBG at age 40y. There was no significant difference in the cumulative BCAA-ASCVD association among men or women who developed DM before ASCVD versus those who did not. Conclusions: Cumulative BCAA exposure in early adulthood is associated with ASCVD in women independent of mid-life BCAA levels. Elevated BCAA levels in women during early adulthood may reflect behaviors and/or metabolic pathways that increase risks for ASCVD independent of the development of hyperglycemia.
Abstract P205: Association of Angptl3/8 and 4/8 With Plasma Metabolites Before and After Exercise Training
Authors: Prasun K Dev, Sebastian Miranda-Maravi, William Hoffman, Jacob L Barber, Charles S Schwartz, William A Clarkson, Jeremy M Robbins, Prashant Rao, Michael Mi, Sujoy Ghosh, Sujoy Ghosh, Clary Clish, Gunther Silbernagel, Yan Q Chen, Robert J Konrad, Claude Bouchard, Robert E Gerszten, Mark A Sarzynski
Journal: Circulation (2023)

Introduction: Angiopoietin like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of lipoprotein lipase and modifiable by regular exercise. However, the molecular underpinning of these novel biomarkers has not been fully elucidated. The purpose of this study was to examine the associations between plasma metabolites and ANGPTL3/8 and 4/8 before and after exercise training. Methods: Measurements were taken before and after 20 weeks of exercise training in 630 adults (36% Black, 56% women, mean age 35 yrs) of the HERITAGE Family Study. Meso Scale Discovery immunoassays were used to measure ANGPTL3/8 and 4/8 in serum. Plasma metabolites (n=300 named) were measured using LC-MS and the HILIC-pos method. Linear mixed models tested the association between metabolites and each trait at baseline and post-training with full covariate adjustment. Significance was set to FDR&lt;0.05. Results: A total of 111 and 93 metabolites were significantly associated with ANGPTL3/8 at baseline or post-training, respectively ( Figure 1A ). A total of 69 metabolites were associated with ANGPTL3/8 at both time points, including ketone bodies, acylcarnitines, and DMGV, while 24 metabolites were only associated at post-training including citric acid, methionine, and glycine. A total of 89 and 40 metabolites were significantly associated with ANGPTL4/8 at baseline or post-training, respectively ( Figure 1B ). A total of 13 metabolites were associated with ANGPTL4/8 at both time points including glycine and lysophospholipids, whereas 27 metabolites were associated only at post-training including hydroxyproline, N-Lignoceroyl Taurine, and methylguanidine. Conclusions: We identified several plasma metabolites associated with ANGPTL3/8 and 4/8 before and after exercise training. Our findings indicate potential metabolic pathways related to the exercise responsiveness of ANGPTL3/8 and 4/8, including glucose-alanine cycle, urea cycle, and glycine and methionine metabolism.
Abstract P428: Evaluating a Personalized Low Sodium Diet Intervention for Blood Pressure Control in Hypertensive Patients: A Pilot Study
Authors: Jisook Ko, Kyungeh An, Jing Wang, Misook L Chung
Journal: Circulation (2023)

Introduction: Although many clinical trials tested the effects of a low sodium diet (LSD) on high blood pressure (HBP) management, adherence to an LSD remains challenging. Considerable barriers to adherence to diet modification have been examined, and heterogenous responses to an LSD evolved. We tested the intra-individual response to an LSD to develop an individualized dietary intervention to optimize HBP management. The purpose of this pilot study was to determine the effectiveness of a personalized low-sodium diet (P-LSD), enhanced by mobile health technology for real-time dietary assessment and at-home BP monitoring in hypertensive adults. Methods: A total of 24 hypertensive patients (60.4±10.7 years) were randomly assigned to either PLSD (n=16) or usual care control groups (n=8). Participants in P-LSD went through individual sessions via video conferencing to discuss LSD regimens, patients’ food choices, and BP tracks on mobile apps. The Control group followed their usual care for HBP management. All participants in both groups monitored diet and BP using mobile apps for 8 weeks. A 24-hour urinary sodium excretion for the estimation of dietary sodium intake, SBP, and DBP were measured at the baseline and at 8 weeks. The preliminary effects of P-LSD were tested by paired t-test and analysis of covariance (ANCOVA). Results: Dietary sodium intake ( t = 3.82), SBP ( t = 3.95), and DBP ( t = 3.54) were significantly declined overtime in the P-LSD group (Ps&lt;0.01) but not in control group (Ps&gt;0.05). There were significant differences between the control and intervention groups in changes of dietary sodium intake (F=18.6, p&lt;0.001) and SBP over time (F=4.84, p&lt;0.05) before and after the intervention. No statistically significant difference was revealed in DBP between the two groups before the intervention (p=0.20). Conclusion: The PLSD appears to be effective on the adherence to an LSD and BP control in hypertensive patients. Future studies with larger sample sizes are warranted to examine the long-term effects of PLSD on outcomes.
Abstract P555: Variants of Neurocan, a Nonalcoholic Fatty Liver Disease Risk Allele, Are Associated With Plaque Development in the Carotid Artery Over 5 Years
Authors: Hiroaki Ikezaki, Ernst J Schaefer, Masayuki Murata, Nobuyuki Shimono
Journal: Circulation (2023)

Introduction: Nonalcoholic fatty liver disease (NAFLD) genetic risk alleles are associated with lipid metabolism. However, the association between those variants and atherosclerosis has not yet been fully evaluated. Hypothesis: We hypothesized that NAFLD risk alleles are associated with the progression of atherosclerosis. Methods: A total of 1,050 Japanese men and women (median age 55 years and median body mass index 22.9 kg/m2) free of cardiovascular disease, dyslipidemia, hypertension, and diabetes were studied. . Among NAFLD risk SNPs, variants of patatin-like phospholipase domain containing 3 ( PNPLA3 ), transmembrane 6 superfamily member 2 ( TM6SF2 ), glucokinase regulator ( GCKR ), and neurocan ( NCAN ) were assessed. Plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL-C, LDL-triglycerides, high-density lipoprotein cholesterol (HDL-C), HDL3-C, triglycerides, remnant-like particle cholesterol, lipoprotein(a), and adiponectin were also measured. At both baseline and after a five-year follow-up, carotid intima-media thickness (cIMT) was assessed. Atherosclerosis was defined as cIMT ≥ 1.1mm or the presence of a plaque. Univariate and multivariate analyses and chi-square and Fisher’s exact tests were performed to examine the associations between NAFLD risk SNPs, lipoproteins, and progression of atherosclerosis. Results: Both median and maximum cIMT of total participants did not differ between baseline and after a five-year follow-up. Among participants without atherosclerosis at baseline, the rate of plaque development was 13.8% (121/880) with the major allele (CC) of NCAN being significantly higher than other alleles. Variants of NCAN were associated with the development of plaque ( P = 0.04, Fisher’s exact test). Participants with the CT allele of NCAN had significantly lower RLP cholesterol at baseline than those with the CC allele (7.6 mg/dl vs. 10.5 mg/dl, P = 0.02). Variants of PNPLA3 , TM6SF2 , GCKR , and NCAN were not associated with changes in lipoproteins. Conclusions: A NCAN variant, one of the NAFLD risk SNPs, was associated with the development of plaque independent of lipoprotein alterations among healthy Japanese participants.
Abstract P302: Midlife Predictors of Extreme Survival Among Israeli Men: A Nested Case-Control Study
Authors: Uri Goldbourt, Yariv Gerber
Journal: Circulation (2023)

Background: Midlife characteristics have been associated with survival to advanced ages. However, the predictive ability of such indicators to distinguish extreme from above-average longevity remains uncertain. We assessed a variety of potential indicators of exceptional vs. above-average longevity in a cohort of working males. Methods: A nested case-control study was conducted within the Israeli Ischemic Heart Disease (IIHD) cohort (n=10,059), consisting of civil servants and municipal employees recruited in 1963 at ages 40-65 years and followed-up for mortality over 55 years (last follow-up, 2019). All participants who survived to age 95 years or more (n=692) were individually matched (1:3) on year of birth to controls who died at ages 80-94 (n=2,076). Sociodemographic, behavioral, clinical, biochemical, and psychosocial data were obtained in 3 study cycles (1963, 1965, and 1968). Logistic regression models were constructed to identify significant predictors of extreme longevity, with over 500 variables screened. Results: Among participants in the IIHD cohort, 52.1% died before reaching 80 years of age, 41.0% survived to age 80-94 years, and 6.9% survived to age 95 years or more [median (IQR) age at death, 79 (70-87) years]. In the case-control analysis, after removal of highly correlated variables, 10 variables were significantly associated with exceptional (95+) longevity (Table). In a multivariable model, education level, low self-perceived employment difficulties, avoiding heavy smoking, maintaining optimal blood pressure and cholesterol levels, and absence of coronary heart disease were the variables most strongly associated with reaching 95 years of age. Conclusions: Using data from a large cohort of male employees assessed during midlife and followed to end of life, we were able to identify a few sociodemographic, lifestyle, clinical, and psychosocial variables associated with extreme longevity, some of which are genetically mediated.
Abstract P139: Behavioral Weight Loss Programs for Cancer Survivors: A Non-Randomized Clinical Trial
Authors: Hsin-Chieh Yeh, Gerald J Jerome, Nae-Yuh Wang, Arlene Dalcin, Linda Bunyard, Nowella Durkin, Jeanne Charleston, Norma Kanarek, Michael Carducci, Lawrence J Appel
Journal: Circulation (2023)

Background: Clinical trials for weight loss in cancer survivors have been shown to be safe and effective. Pragmatic approaches are needed to facilitate broader adoption. The ASPIRE study evaluates real-world, lifestyle weight loss programs in Maryland on reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) outcomes. Here we report 6-month data on weight change. Methods: Participants were adults with overweight or obesity, who had a history of solid malignant tumors and completed curative intent treatment. The exclusion criteria were minimized to increase generalizability. Participants self-selected 1 of 3 programs: the Self-Directed (SD) Program provided evidence-based, written materials; the App-Directed (AD) Program additionally provided a commercially available, free smartphone app and weekly diet and exercise tips; and the Coach-Directed (CD) Program additionally included 1-on-1 telephonic coaching. SD and AD had versions with and without weight tracking; CD required weight tracking. Weights were transmitted to the study team using cellular technology with the scales provided and collected at baseline, 3, 6, and 12 months. Results: 5,644 cancer survivors were invited, mostly via electronic health records; 9% expressed interest. Of these, 67% enrolled (total n=340; n=240 in weight tracking programs; 54% black, 74% women.) Participants in CD were younger, more likely to be women, less likely to have bachelor’s degree, and weighed more than those in SD. At 6m, weights were obtained from 97.5% of participants. Within-program weight reduction was most significant in CD. In the adjusted mixed-effects models, compared with SD participants, CD participants achieved significant weight reduction (see Table) Conclusion: Remotely delivered weight loss programs are desirable and can be broad- reach. Intervention with remote coaching was effective. While selected by many participants, app-directed program with weight tracking but without coaching led to small weight reduction.
Abstract P321: Prevalence of Hypertension Among People Diagnosed With Diabetes in Africa, a Systematic Review and Meta-Analysis
Authors: Thomas Hinneh, Samuel Akyirem, Irene F Bossman, Patriot Ofori-Aning, Victor Lambongang, Oluwabunmi V Ogungbe, Yvonne Commodore-Mensah
Journal: Circulation (2023)

Background: Hypertension (HTN) and diabetes (DM) share common pathophysiological mechanisms and hence have a high likelihood of co-occurring. The co-existence of HTN and DM increase increases CVD risk and exponentially increases health spending. Little is known about the burden of HTN in people with DM in Africa. Objective: To estimate the pooled prevalence of HTN in people with DM in African countries. Methods: This review was registered in the International Prospective Register of Systematic Reviews. We searched PubMed, Embase, and Hinari databases to identify peer-reviewed articles which provided data on the prevalence of HTN in people diagnosed with DM in Africa. We included studies that defined DM diagnosis as hemoglobin A1(HbA1c) &gt;7.0 and HTN diagnosis as BP≥140/90mmHg. We quantified the prevalence of HTN using random-effects models. We applied generalized linear mixed models with logit transformation to compute regional and overall pooled prevalence and estimated heterogeneity (I 2 ). Results: Out of 3810 studies retrieved from the databases, 27 met the inclusion criteria with sample size between (80 - 4122). The mean age was 58 (± 11) years and 56% were women. The pool prevalence of HTN in people diagnosed with DM was 59.8% [95% CI: 52.8% - 66.5%]. By African region, Central Africa recorded the highest 77.6% [95% CI: 53.01% - 91.4%], South Africa 74.5% [95% CI: 67.4% - 80.5%], North Africa 65.5% [95% CI: 54.7% - 75.0%], West Africa 55.7% [95% CI: 44.0% - 66.7%] and East Africa 50.7% [95% CI: 43.7% - 57.3%]. Increasing age, being overweight/obese, being employed, longer duration of DM, urban residence, and male sex were associated with a higher likelihood of HTN diagnosis. Conclusion: The high prevalence of HTN among people with DM in Africa, supports an integrated differentiated service delivery to improve primary healthcare-level cardiovascular disease response mechanisms. The data generated from this review may inform the delivery of interventions to avert premature cardiovascular disease mortality among Africans.
Abstract 61: Frequency of Pediatric Lipid Screening Using a Large National Electronic Health Record System
Authors: Angela M Thompson-Paul, Emily Kraus, Renee M Porter, Samantha L Pierce, Lyudmyla Kompaniyets, Ahlia Sekkarie, Alyson B Goodman, Sandra L Jackson
Journal: Circulation (2023)

Background: Universal lipid screening is recommended for U.S. youth aged 9-11 and 17-21 years. Our objective was to describe the prevalence of pediatric lipid screening and elevated lipid measurements among those screened, by patient characteristics. Methods: IQVIA’s Ambulatory Electronic Medical Records (version 5, release: October 2021) database, containing medical records from 100,000 physicians in the U.S., was used for this analysis. The study population included 3,131,956 patients aged 9-21 years with ≥1 valid measure of height and weight during our observation period (01/01/2018-11/30/2021). Lipid screening was defined as ≥1 valid measurement any time during the observation period. Body mass index (BMI) was calculated and categorized using pediatric percentiles (ages 9-20 years) and adult interpretations (age ≥21 years) ( Table ). After excluding biologically implausible values, lipid measurements were considered elevated if ≥1 of the following was identified: low density lipoprotein ≥130 mg/dL, very low-density lipoprotein ≥31 mg/dL, non-high-density lipoprotein ≥145 mg/dL, triglycerides ≥130 mg/dL, or total cholesterol ≥200 mg/dL. Results: A total of 354,764 (11.3%) youth had documented lipid screening. The frequency of lipid screening increased by age group (9-11 years: 9.1%; 12-16 years: 11.0%,17-21 years: 12.9%) and BMI category (underweight and healthy weight: 9.5%; overweight: 11.0%; obesity: 16.7%; severe obesity: 19.6%). Frequency of screening varied across race/ethnicity (White: 10.8%; Black 14.5%; Asian: 18.0%). Among those screened, 30.2% had ≥1 elevated measure with highest prevalence among those with obesity (44.8%) or severe obesity (48.1%). Conclusions: Our findings indicate that among youth aged 9-11y and 17-21y, lipid screening is suboptimal, and prevalence of elevated lipid levels is high among those screened. Increased pediatric lipid screening could lead to improvements in treatment, management, and prevention of adverse, long-term cardiovascular outcomes.